1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVolinanserinCat. No.: HY-14940CAS No.: 139290-65-6Synonyms: MDL100907; M 100907分式: CHFNO分量: 373.46作靶點: 5-HT Receptor作通路: GPCR/G Protein; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性

2、數據體外實驗 DMSO : 106.6 mg/mL (285.44 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.6777 mL 13.3883 mL 26.7766 mL5 mM 0.5355 mL 2.6777 mL 5.3553 mL10 mM 0.2678 mL 1.3388 mL 2.6777 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄清的儲備液，再依次添加助溶劑(為保

3、證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄清的儲備液可以根據儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.69 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.69 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90

4、% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (6.69 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Volinanserin種有效的，選擇性的 5-HT2 受體拮抗劑，Ki 值為 0.36 nM，對其選擇性是對 5-HT1c，alpha-1 和 DA D2 受體的 300 倍，可于精神疾病的研究。IC50 & Target Ki: 0.36 nM (5-HT2 receptor) 1體外研究 Volinanserin (MDL 10090

5、7) is a potent antagonist at the 5-HT2 receptor, with a Ki of 0.36 nM, and shows300-fold selectivity for 5-HT2 receptor over 5-HT1c receptor, alpha-1 and DA D2 receptors. Volinanserin hasantipsychotic activity 1.體內研究 Volinanserin (MDL 100907; 0.008-2.0 mg/kg, i.p.) significantly decreases d-amphetam

6、ine-stimulatedlocomotor activity in mice, with an ED50 of 0.3 mg/kg, but shows no obvious reduction in the base-linelocomotor activity in mice. Volinanserin produces atalepsy with an ED50 of 10-50 mg/kg in rats. Volinanserindoes not reduces apomorphine-induced stereotypies or produces catalepsy in r

7、ats 1. Volinanserin(M100907) combined with MK-801 significantly decreases reinforcers at 1 g/kg, but dose-dependently (10,100 g/kg) antagonizes the disruptive effect of MK-801 in rats via i.p. administration. Volinanserin (6.25 g/kg) enhances the antidepressant-like action of desipramine in rats per

8、forming under a DRL 72-s schedule,and elevates the antidepressant-like effect of tranylcypromine 2.PROTOCOLAnimal Mice 1Administration 1 To measure the effects the test compounds alone on spontaneous locomotor activity, mice are injected i.p.with the test compounds, placed singly into clear Plexigla

9、s test cages (16 16 8 inches) and are allowed toacclimatize for 30 mm. Six mice per dose for each of the six doses are tested for Volinanserin (0.008-2.0mg/kg), amperozide and haloperidol. Twelve mice per dose for six doses are tested for clozapine. Sixtyanimals are given vehicle in these experiment

10、s. Thereafter, the boxes are placed in the activity monitors andmeasurements are taken for 30 mm. To measure the effects of various pretreatments on amphetaminestimulated motor activity, mice (four per test box) are acclimatized for 90 mm to reduce the level ofspontaneous activity of the controls. T

11、he mice are then injected with amphetamine (2 mg/kg i.p.) as well asthe test compounds, returned to the activity boxes and tested for 90 mm. In these experiments 16 mice perdose are tested for the 9 doses of Volinanserin and 16 mice per dose are tested for each of 6 doses foramperozide, clozapine an

12、d haloperidol. One hundred forty four mice received vehicle in these experiments1.Rats 1Drugs and doses used are clozapine (1, 10 and 50 mg/kg) or Volinanserin (1, 10 and 50 mg/kg), amperozide(1, 10 and 50 mg/kg) and haloperidol (0.1, 0.3 and 1.0 mg/kg). Five rats per dose are used in theseexperimen

13、ts and five rats receive vehicle. Rats are dosed i.p. and, 30 mm later, each rat is placed gently intoa clear Plexiglas enclosure (30 30 15 cm) so that both front limbs rested on top of a horizontal aluminum2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemErod (1.2 cm in diameter). The rod is centere

14、d across the plastic enclosure at a height of 7 cm above the floor.The time each rat remained with its hind legs on the floor while the front limbs are elevated on the rod isrecorded to the nearest second. Data are analyzed by using analysis of variance followed by appropriatepost-hoc tests 1.MCE ha

15、s not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Sorensen SM, et al. Characterization of the 5-HT2 receptor antagonist MDL 100907 as a putative atypical antipsychotic: behavioral,electrophysiological and neurochemical studies. J Pharmacol Exp Ther

16、. 1993 Aug;266(2):684-91.2. Ardayfio PA, et al. The 5-hydroxytryptamine2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-2-(4-fluorophenyl)ethyl-4-piperidinemethanol (M100907) attenuates impulsivity after both drug-induced disruption (dizocilpine) and enhancement (antidepressantdrugs) of differential-reinforcement-of-low-rate 72-s behavior in the rat. J